PB2059: SUCCESSFUL OUTCOME OF A PATIENT WITH ADVANCED SYSTEMIC MASTOCYTOSIS TREATED WITH AZACYTIDINE AND AVAPRITINIB: A CASE REPORT
Authors: C. Saha, V. Stables, E. Dimitriadou, J. Schofield, A. Green, D. Radia
Journal: HemaSphere (2022)

Background: Systemic mastocytosis (SM) with an associated hematologic neoplasm (AHN) comprise approximately 70% of patients with Advanced SM (AdvSM). >80% of patients with SM-AHN have associated myeloid neoplasms: CMML being common. The median overall survival of patients with SM-CMML is reported to be 15 months. Current algorithms for patients with SM-AHN direct treatment to each of the components tailored to the patient. Avapritinib,a C-KIT tyrosine kinase inhibitor, approved by the FDA in 2021 for patients with AdvSM has an overall response rate of 70% as reported in early phase trials. Aims: To report successful treatment of advanced SM: SM+CMML, both components requiring treatment simultaneously. Methods: A retrospective review of a case (with patient consent). Results: A 58yr old previously fit male was seen in July 2019 with urticaria pigmentosa, recent significant weight loss & mild hepatosplenomegaly. Initial blood counts:hemoglobin(Hb) 123g/L;leukocytes(WBC) 32.6x109/L;platelets(PLT) 123x109/L;neutrophils 20.5x109/L;lymphocytes 3.3x109/L;monocytes 4.2x109/L;eosinophil 0.7x109/L and normal biochemistry. His MC Tryptase was 54.4µg/L. JAK2 V617F & C-KIT D816V mutations was detected. A diagnostic bone marrow trephine(BM) in July 2019 was >90% cellular with marked granulocytic proliferation, hypolobated megakaryocytes, peritrabecular spindle shaped mast cells(10%) positive for CD117 and CD25 immunostains &focal fibrosis of WHO grade 0-1,with diagnosis of SM with CMML. Cytogenetics were normal. Myeloid gene panel detected high risk mutations (TET2 x2, SRSF2). He initially declined treatment. By October 2020, he had intense pruritus, further weight loss, night sweats, bone pain, progressive hepatosplenomegaly, small volume generalised lymphadenopathy, mild ascites & progressive cytopenias (Hb 60g/L & PLT 43x109/L), leucocytosis(WBC 48.9x109/L) & MC tryptase of 105µg/L. Repeat BM showed MC burden of 15-20% (MC tryptase+, CD117+, CD25+) in a hypercellular marrow with predominant increase in granulopoiesis with 20% monocytic cells(CD14+), no increase in CD34+ cells: consistent with evidence of progression of both components. He was treated with azacytidine to debulk the CMML component due to progressive cytopenias and leucocytosis. His PLT count of < 50 x 109/L precluded eligibility onto the PATHFINDER trial due to a risk of intracranial haemorrhage. After 3 cycles, his blood counts improved (Fig 1) and correction of thrombocytopenia (PLT 282 x109/L) allowed treatment of the SM component by avapritinib via Compassionate Access Programme and he started avapritinib 200mg daily. He had rapid symptom improvement with resolution of ascites, hepatosplenomegaly & lymphadenopathy. BM post 4 cycles of avapritinib showed complete remission of SM with persistent CMML-0. MC tryptase normalised to 7.4 µg/L with WBC slowly rising again off azacitidine(Fig 1). He is currently asymptomatic on 100mg of avapritinib. Image:Summary/Conclusion: This patient needed treatment of symptoms predominantly due to SM; thrombocytopenia precluded treatment with avapritinib. The CMML component was treated first to improve thrombocytopenia with azacytidine followed by avapritinib for the SM component. The outcome was excellent with complete remission of his SM component & marked clinical improvement. The patient can be considered for an allogeniec bone marrow transplant as a curative treatment. International trials with sequential/combination therapy for patients with AdvSM in the new era of targeted C-KIT inhibitors will inform better treatment decisions for patients with SM-AHN.